Reducing the extent of secondary degeneration following spinal cord injury (SCI) is necessary to preserve function, but treatment options have thus far been limited. A combination of the ion channel inhibitors Lomerizine (Lom), YM872 and oxATP, to inhibit voltage-gated Ca²⁺ channels, Ca²⁺ permeable AMPA receptors, and purinergic P2X₇ receptors respectively, effectively limits secondary consequences of injury in in vitro and in vivo models of CNS injury. Here, we investigated the efficacy of these inhibitors in a clinically relevant model of SCI. Fischer (F344) rats were subjected to a moderate (150 kD) contusive SCI at thoracic level T10 and assessed at 2 weeks or 10 weeks post-injury. Lom was delivered orally twice daily and YM872 and oxATP were delivered via osmotic mini-pump implanted at the time of SCI until 2 weeks following injury. Open field locomotion analysis revealed that treatment with the three inhibitors in combination improved the rate of functional recovery of the hind limb (compared to controls) as early as 1-day post-injury, with beneficial effects persisting to 14 days post-injury, while all three inhibitors were present. At 2 weeks following combinatorial treatment, the functional improvement was associated with significantly decreased cyst size, increased immunoreactivity of β-III tubulin^+ve axons, myelin basic protein, and reduced lipid peroxidation by-products, and increased CC1^+ve oligodendrocytes and NG2^+ve/PDGFα^+ve oligodendrocyte progenitor cell densities, compared to vehicle-treated SCI animals. The combination of Lom, oxATP, and YM872 shows preclinical promise for control of secondary degeneration following SCI, and further investigation of long-term sustained treatment is warranted.

减少脊髓损伤（SCI）后继发性变性的程度对于保持功能是必要的，但是迄今为止，治疗选择受到了限制。离子通道抑制剂Lomerizine（Lom），YM872和oxATP的组合分别抑制电压门控性Ca ²⁺通道，Ca ²⁺渗透性AMPA受体和嘌呤能P2X ₇受体，有效地限制了损伤的继发性后果。体外 和 体内中枢神经系统损伤模型。在这里，我们在临床相关的SCI模型中研究了这些抑制剂的功效。将Fischer（F344）大鼠在胸廓T10处接受中度（150 kD）挫伤性SCI，并在受伤后2周或10周进行评估。每天两次口服Lom，并递送YM872和oxATP通过SCI时植入渗透性微型泵直至受伤后2周。开阔运动分析表明，在受伤后1天，三种抑制剂联合治疗可提高后肢的功能恢复率（与对照组相比），有益效果持续至受伤后14天，而所有三种抑制剂均存在。组合治疗后2周，功能改善与囊肿大小明显减少，β-III微管蛋白^{+ ve}轴突，髓鞘碱性蛋白的免疫反应性增加，脂质过氧化副产物减少以及CC1 ^{+ ve}少突胶质细胞和NG2 ⁺增多有关。^ve /PDGFα ^{+ ve}与媒介物处理的SCI动物相比，少突胶质祖细胞密度。Lom，oxATP和YM872的组合显示出临床前有望控制SCI后继发性变性，因此有必要对长期持续治疗进行进一步研究。